Global Health: They Swallowed Live Typhoid Bacteria — On Purpose
It is the only effective vaccine that is also safe for infants, and already it is made cheaply and used widely in India. The Oxford Vaccine Group, which ran the trial, and the Bill & Melinda Gates Foundation, which paid for it, hope the World Health Organization will endorse the vaccine soon.
“These are great results,” said Dr. Anita Zaidi, the foundation’s director of diarrheal diseases. “And challenge tests are a great way to short-circuit the process of proving it works.
“If we’d done this in the field, we would have had to follow children for three or four years.”
So-called challenge tests involve giving subjects an experimental vaccine and then deliberately infecting them with the disease to see if it protects them.
These tests can only be done with illnesses — like cholera or malaria — that can be rapidly and completely cured, or with diseases — like seasonal flu — that normally do not damage healthy adults.
Still, there was a good chance that the participants in Oxford would be unpleasantly sick with typhoid fever for several days until their antibiotics kicked in.
So what would motivate dozens of well-educated Britons to swallow a vial full of the germs that made Typhoid Mary famous? In interviews, they gave various reasons.
Some, like Mr. Duggan, were curious. Some wanted to help poor people. And some mostly wanted the cash.
Participants who followed all the steps, which included recording their temperatures online, making daily clinic visits and providing regular blood and stool samples, received about $4,000.
They all said they understood the risks.
Typhoid got its fearsome reputation in the pre-antibiotic age, but these days it normally can be driven out of the body with common antibiotics, like ciprofloxacin or azithromycin.
All participants had to be healthy adults, ages 18 to 60, with ultrasound scans proving their gallbladders were stone-free.
(The bacteria can persist for decades by clinging to gallstones — which is probably how Typhoid Mary, working as a cook in grand houses and a maternity hospital, infected so many people between 1900 and 1915 without ever feeling ill herself.)
Different participants had very different experiences.
Mr. Duggan was sick for three days with flulike symptoms: “proper flu, where you don’t want to get out of bed,” he said. His temperature rose to 102 degrees, and he had joint pains and a bad headache.
Once a blood culture proved he had typhoid, he got antibiotics right away; he was not released from treatment until three typhoid-free blood and stool samples proved he was out of danger.
He later was told that he had been in the trial’s placebo arm and had received a meningitis vaccine instead. (Modern ethics boards frown on useless “sugar pill” placebos.)
Nick J. Crang, 24, a graduate student in proteomics, also got the placebo. But somehow he never got sick, even after two typhoid challenges a year apart.
“It turns out I’ve got innate immunity to typhoid,” he said.
So does he feel superhuman? “No, I’m the lab rat who’s screwing with the figures.”
He did give extra blood samples to researchers curious about his immune system.
The bacterial doses were offered by nurses wearing plastic aprons, gloves and face shields to prevent splashing. Participants also donned aprons and goggles, and were asked to first drink bicarbonate of soda to neutralize their stomach acid.
But there were no steaming beakers out of Vincent Price movies. “It was all quite underwhelming,” said Daina Sadurska, 26, a grad student in biology. “It was served in a typical laboratory tube. I expected it to taste more ‘typhoidy.’ Not like poop, that is – the things that make poop smell like poop are absolutely different bacterially.”
“But I expected something. A lot of cultures have a typical smell. It was clear, I think, and it tasted like nothing particular.”
Ms. Sadurska never fell ill and later learned that she had gotten the vaccine. She had a unique reason for joining: her great-great-grandmother and one of her aunts died during a typhoid epidemic in Latvia during World War I.
“When I told my mother I was doing this, she reminded me of that episode,” she said. “When I signed up, I thought, ‘Why on Earth am I doing this?’ But I’m a biologist. All sorts of boogeymen become a lot less scary when you know more about them.”
The $4,000 was also “a welcome addition,” she said. Oxford students get only $17,600 a year to live in a city with costs almost as high as London’s.
She and Mr. Crang, her boyfriend, used the money to visit Croatia, Israel and her family in Latvia. They have both signed up for a second vaccine trial that will pay for his laser eye surgery and then a trip together to Australia.
Faye Francis, a 42-year-old psychiatric nurse, said she felt “happy to be doing something that could help millions of poor people who haven’t got antibiotics.”
“But I won’t lie,” she added. “The money was a big part of it.”
She used it to take her husband and three children on a vacation in Cornwall “and buy a few bits for the car and the house.”
Her mother was not happy. “She said, ‘That’s ridiculous – don’t think about the money, think about your health!’ ” Mrs. Francis said. “And people were telling me horror stories about things they’d seen on TV. So I didn’t go on about it to my parents after that.”
She got sick and “felt rotten for about a week” with a 101-degree fever, headache and nausea.
“But I still went to work,” she said. “I felt a bit guilty about not going when I had an illness I’d given myself.”
Because her job is to distribute medicine on home visits, no patients were endangered, she said. (Mr. Duggan, the medical student, was also quick to say that he took part during a period when he was not assigned to hospital rounds.)
“They don’t let you do it if you’ve got preschoolers or children in nappies,” Mrs. Francis said. “And you’re not allowed to handle food, so my husband did all the cooking.”
During the worst week, “you feel sorry for yourself and you say ‘I’m never doing that again,’ ” she said. “And then it’s like childbirth – you get amnesia, and you do it again. I’ve just signed up for a second trial.”
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